Two curcumin analogs inhibited the function and protein expression of breast cancer resistance protein: in vitro and in vivo studies

Abstract

1. Two curcumin analogs, (1E,6E)-1,7-bis(3,5-diethyl-4-hydroxyphenyl)hepta-1,6-diene-3,5- dione (N17) and its prodrug ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2,6-diethyl-4,1- phenylene)bis(3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate) (N17′), were evaluated as breast cancer resistance protein (BCRP) inhibitors.

2. MDCKII-BCRP and MDCKII-WT were used to evaluate the modulation effects of N17 and N17′ on BCRP and to explore the relevant mechanism. Sprague-Dawley rats were orally administered rosuvastatin (ROS), a probe substrate of BCRP, without and with N17′ (100 mg/kg) to investigate the effect of N17′ on ROS pharmacokinetics.

3. In cell studies, N17 and N17′ were substrates of BCRP, and they decreased the activity and protein expression of BCRP. In rat study, N17′ increased the systemic exposure of ROS by 218% (p = 0.058).

4. N17 and N17′ are potential BCRP inhibitors and will be promising candidates for overcoming the BCRP-mediated multidrug resistance.

Keywords:

• Curcumin analogs
• multidrug resistance
• Breast cancer resistance protein
• ATP-binding cassette transporters
• rosuvastatin

Disclosure statement

The authors have declared no conflict of interest.

Additional information

Funding

This work was supported by the Ministry of Science and Technology, Taiwan, ROC under Grant [MOST 108-2320-B-039-041-MY3, MOST 111-2320-B-039-048]; China Medical University, Taiwan, ROC under Grant [CMU110-S-06]; China Medical University Hospital, Taiwan, ROC under Grant [DMR-108-146]; and ‘Chinese Medicine Research Center, China Medical University’ from the Featured Areas Research Centre Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan under Grant [CMRC-CHM-3-2].